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Sökning: onr:"swepub:oai:lup.lub.lu.se:a28a0372-b29f-418b-bd5b-9bdb8f008063" > A genomic explorati...

A genomic exploration identifies mechanisms that may explain adverse cardiovascular effects of COX-2 inhibitors

Brænne, Ingrid (författare)
University of Lübeck, Institute for Cardiogeneticss; DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Lübeck
Willenborg, Christina (författare)
University of Lübeck, Institute for Cardiogeneticss
Tragante, Vinicius (författare)
University Medical Center Utrecht, Division Heart and Lungs, Department of Cardiology
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Kessler, Thorsten (författare)
Technical University of Munich,German Centre for Cardiovascular Research,Technische Universität München, Deutsches Herzzentrum München
Zeng, Lingyao (författare)
Technical University of Munich,German Centre for Cardiovascular Research,Technische Universität München, Deutsche s Herzzentrum München
Reiz, Benedikt (författare)
University of Lübeck, Institute for Cardiogeneticss; DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Lübeck,German Centre for Cardiovascular Research
Kleinecke, Mariana (författare)
University of Lübeck, Institute for Cardiogeneticss; DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Lübeck,German Centre for Cardiovascular Research
Von Ameln, Simon (författare)
German Centre for Cardiovascular Research,Technical University of Munich,Technische Universität München, Deutsches Herzzentrum München
Willer, Cristen J (författare)
University of Michigan, Dept of Biostatistics
Laakso, Markku (författare)
University of Eastern Finland and Kuopio University Hospital, Internal Medicine, Institute of Clinical Medicine
Wild, Philipp S. (författare)
Universitätsmedizin Mainz,University Medical Center Mainz, Preventive Cardiology and Preventive Medicine; University Medical Center Mainz, Center for Thrombosis and Hemostasis; DZHK (German Center for Cardiovascular Research), Partner Site RhineMain
Zeller, Tanja (författare)
University Medical Center Hamburg-Eppendorf,DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Hamburg-Eppendorf, Department of General and Interventional Cardiology
Wallentin, Lars, 1943- (författare)
Uppsala universitet,Kardiologi
Franks, Paul W. (författare)
Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Lund University, Skåne University Hospital Malmö, Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit
Salomaa, Veikko (författare)
Finnish National Institute for Health and Welfare,THL-National Institute for Health and Welfare, POB 30, Mannerheimintie 166, FI-00271, Helsinki
Dehghan, Abbas (författare)
Erasmus University Medical Center, Department of Epidemiology
Meitinger, Thomas (författare)
Erasmus University Medical Center, Department of Epidemiology; German Research Center for Environmental Health, Helmholtz Zentrum München, Institute of Human Genetics; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance; Technische Universität München, Institute of Human Genetics,Helmholtz Zentrum München,Technical University of Munich
Samani, Nilesh J. (författare)
University of Leicester, Deparment of Cardiovascular Sciences; Glenfield Hospital, NIHR Leicester Cardiovascular Biomedical Research Unit
Asselbergs, Folkert W (författare)
University Medical Center Utrecht, Division Heart and Lungs, Department of Cardiology; University College London, Faculty of Population Health Science, Institute of Cardiovascular Science
Erdmann, Jeanette (författare)
University of Lübeck, Institute for Cardiogeneticss; DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Lübeck,German Centre for Cardiovascular Research
Schunkert, Heribert (författare)
Technical University of Munich,German Centre for Cardiovascular Research,Technische Universität München, Deutsches Herzzentrum München; German Research Center for Environmental Health, Helmholtz Zentrum München, Institute of Human Genetics
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 (creator_code:org_t)
2017-08-31
2017
Engelska.
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
Relaterad länk:
http://dx.doi.org/10... (free)
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https://www.nature.c...
https://doi.org/10.1...
https://uu.diva-port... (primary) (Raw object)
https://lup.lub.lu.s...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Cyclooxygenase-2 inhibitors (coxibs) are characterized by multiple molecular off-target effects and increased coronary artery disease (CAD) risk. Here, we systematically explored common variants of genes representing molecular targets of coxibs for association with CAD. Given a broad spectrum of pleiotropic effects of coxibs, our intention was to narrow potential mechanisms affecting CAD risk as we hypothesized that the affected genes may also display genomic signals of coronary disease risk. A Drug Gene Interaction Database search identified 47 gene products to be affected by coxibs. We traced association signals in 200-kb regions surrounding these genes in 84,813 CAD cases and 202,543 controls. Based on a threshold of 1 × 10-5 (Bonferroni correction for 3131 haplotype blocks), four gene loci yielded significant associations. The lead SNPs were rs7270354 (MMP9), rs4888383 (BCAR1), rs6905288 (VEGFA1), and rs556321 (CACNA1E). By additional genotyping, rs7270354 at MMP9 and rs4888383 at BCAR1 also reached the established GWAS threshold for genome-wide significance. The findings demonstrate overlap of genes affected by coxibs and those mediating CAD risk and points to further mechanisms, which are potentially responsible for coxib-associated CAD risk. The novel approach furthermore suggests that genetic studies may be useful to explore the clinical relevance of off-target drug effects.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

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